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bioRxiv · 10.64898/2025.12.12.692552

Single-cell whole-genome sequencing reveals convergent evolution in Burkitt lymphoma

Steemers, A. S.·van Roosmalen, M. J.·Hagelaar, R.·Trabut, L.·Verheul, M.·Jongsma, S.·de Kanter, J. K.·Meyer-Wentrup, F.·van Boxtel, R.
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Abstract

Burkitt lymphoma (BL) carries multiple oncogenic drivers yet arises predominantly in children, whose normal cells harbour few age-related mutations. To investigate this paradox, we sought to define the sequence and timing of mutational drivers underlying BL development. Here, we analysed single-cell whole-genome sequencing (WGS) data of 250 paired normal and malignant B-cells from BL patients and integrated this data with 21 bulk WGS samples and an existing dataset of 157 clonally expanded B-cells from healthy individuals. Phylogenetic reconstruction revealed an accelerated accumulation of mutations following the emergence of the most recent common ancestor, leading to the early establishment of extensive genetic intra-tumoral heterogeneity. We further provide evidence that convergent evolution shapes this diversity at both the point mutation- and copy number variation-levels. This in-depth characterisation further establishes BL as a paradigmatic model of tumorigenesis with implications for therapeutic intervention.

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Steemers, A. S., van Roosmalen, M. J., Hagelaar, R., Trabut, L., Verheul, M., Jongsma, S., de Kanter, J. K., Meyer-Wentrup, F., van Boxtel, R.. 2025-12-14. Single-cell whole-genome sequencing reveals convergent evolution in Burkitt lymphoma. https://doi.org/10.64898/2025.12.12.692552

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